Daniel I. H. Linzer
The interest of the laboratory is on the development and function of the placenta. Current studies aim to identify the physiological roles of novel placental hormones, and to characterize the steps leading from the trophectoderm, the first differentiated cell type to form in the blastocyst, to the various trophoblast cell types that constitute the placenta.
The development of the mammalian fetus within the mother requires that mammalian reproduction and development be tightly linked. Changes in maternal physiology must occur to accommodate and nurture the fetus. The "master regulator" of these changes is the placenta, the major endocrine organ of pregnancy and the source of many pregnancy-specific hormones. Among these placental hormones are proteins closely related to pituitary prolactin, but most of these placental hormones have molecular and cellular targets and physiological functions distinct from prolactin. We have found that two of the placental hormones are respectively positive and negative regulators of angiogenesis, providing balancing activities to regulate the formation of the nutrient and waste exchange system. We have found that other hormones regulate hematopoiesis. By identifying and characterizing novel physiological regulators of pregnancy, we anticipate that novel receptors and signaling pathways will be revealed that act on the mother and fetus.
These hormones also provide markers for specific stages of placental development. Genes encoding these hormones are exquisitely regulated with respect to the day of pregnancy and the site of expression within the placenta. Characterization of how these hormone genes are controlled should reveal key factors that regulate the broader program of placental development. The placenta is unique in the formation of intimate cell-cell contacts between genetically distinct (maternal and extra-embryonic) tissues, its rapid remodeling during pregnancy, and its transience. Proper development of the placenta is essential for embryonic development, for without the placenta the embryo would be unable to attach to the uterus, it would be unable to obtain nutrients and discard wastes, and it would be subject to attack by the maternal immune system. Since the placenta forms from the first cells to differentiate in the mammalian embryo, the characterization of how the placenta develops will also provide a window on how the earliest cell fate decisions are made in mammalian embryogenesis.